Rita Cowell, Ph.D.

A fine balance between excitation and inhibition is required for higher cognitive function. Inhibitory interneurons that express the calcium buffer parvalbumin are critical regulators of neuronal excitability in the cortex; as such, any alterations in their function can disrupt cognition and motor function. In the Cowell lab, we have discovered that the expression of parvalbumin and the function of these inhibitory interneurons are dependent on the transcriptional coactivator PGC-1α (peroxisome proliferator activated receptor γ coactivator 1α) and that cell-specific deletion of PGC-1α in the brain results in very interesting molecular and behavioral phenotypes. To determine how the loss or overexpression of PGC-1α influences the brain circuits for movement, learning, and memory, the lab uses a number of techniques including immunofluorescence and confocal microscopy, quantitative RT-PCR, electrophysiology, and behavioral tests of memory and motor function in knockout mice and mouse models of disease. As there is evidence for reduced PGC-1α function in neurological disorders such as Parkinson and Huntington Diseases and alterations in excitatory-inhibitory balance in neurodevelopmental disorders such as Tourette syndrome, epilepsy, and schizophrenia, by understanding PGC-1α’s roles in the brain, we can begin to design therapeutic approaches to modulate PGC-1α function directly in the brain, rescuing behavioral impairment in different brain disorders.